Structural changes in glaucoma occur in the retina, optic nerve head, retrobulbar optic nerve, lateral geniculate nucleus, and visual cortex. Among these structures, the lamina cribrosa (LC) is considered as the primary site of retinal ganglion cell axonal injury in glaucoma.1–7 Therefore, in addition to clinical examination of optic disc and peripapillary region, evaluation of the LC structure may enhance diagnostics and understanding of glaucoma pathophysiology. However, only the superficial portion of the central LC is clinically seen through the thin prelaminar tissue, and the LC is mostly obscured by the neuroretinal rim in the disc region and by the scleral rim, choroid, and retinal pigment epithelium in the parapapillary region. Posterior displacement of the LC was demonstrated in histological studies in non-human primate models of glaucoma7–9 and postmortem eyes,2,4,5,10,11 but histological processing may alter the architecture seen in vivo.
The LC is a mesh-like structure in the scleral canal of the optic nerve head composed of overlapping and branching collagenous beams.12–14 Enhanced depth imaging optical coherence tomography (EDI OCT) improves in vivo visualization of the LC in human eyes.15–17 The depth of the LC was measured with the Bruch’s membrane opening as a reference plane, demonstrating that the LC depth was significantly deeper (more posteriorly displaced) in glaucoma patients than in healthy subjects.18 Since mathematical models of the optic nerve head consistently predict regions of relatively large mechanical strain in the peripheral LC, the LC insertion area was investigated in detail. Yang et al19 measured the position of LC insertion site before and after inducing glaucomatous damage by increasing the intraocular pressure (IOP) and revealed that posterior (outward) migration of the LC insertion is a component of early cupping in monkey experimental glaucoma model. The LC thickness was also investigated using EDI OCT in glaucoma. Measurement of the LC thickness showed that the LC was thinner in glaucoma patients than in healthy subjects, and in normal-tension glaucoma than in high-tension glaucoma.20 This study also demonstrated that the LC becomes thinner as glaucoma advances and reaches a plateau.
The above studies described general morphologic changes of the LC such as laminar thinning and posterior laminar displacement in glaucoma, not localized LC changes. Focal defects of the LC (Fig. 1) of varying size and shape were reported in glaucoma using EDI OCT, and focal laminar defects appear to be a characteristic feature of the glaucomatous optic nerve head.21 Therefore, structural changes in the LC in glaucomatous eyes occur in both generalized and localized fashions.
It can be postulated that these changes may have different underlying mechanisms. Generalized changes in the LC structure may be associated with the LC’s initial response and subsequent remodeling to elevated IOP that theoretically exerts a uniform load on the LC. Because of regional variation in the LC architecture,2,3,17 however, local mechanical stress and strain within the LC are inhomogeneous and correlated with local laminar density.22 Therefore, chronic exposure to elevated IOP may lead to localized changes in the LC structure in addition to generalized changes, especially in the inferior and superior LC periphery which tends to contain larger LC pores and thinner connective tissue.2,23 Either generalized or localized LC changes may predominate in some glaucomatous eyes, depending on the age of disease onset, acute or chronic nature of the disease, duration of the disease, baseline structural characteristics of the LC, or variations in local blood perfusion, all of which need further investigations.
In conclusion, a variety of structural LC changes occur in glaucoma and EDI OCT is a commercially available method that can be used for in vivo evaluation of these changes, which are often clinically invisible. More sophisticated imaging devices including those using swept-source OCT or adaptive optics technologies would help earlier and more accurate detection of the LC deformation.
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